The complete DNA sequences of the genome of Rickettsia typhi will be determined and analyzed for putative coding regions and possible functions of the gene products. Under an addendum for potential bioterrorism agents of the Policy on Support of Large- Scale Genome Sequencing Projects, R. typhi has been designated as a priority bioterrorism agent. This application is prepared in response to this opportunity for support of large-scale genome sequencing of high priority pathogens as potential agents of bioterrorism. Rickettsia typhi is highly infectious, including via aerosol exposure, infection is deceptively difficult to diagnose clinically and causes a severe, incapacitating illness with 1 percent overall mortality. Knowledge of its genome would be most useful for comparison with that of the more virulent R. prowazekii and for investigation of virulence factors, targets of attenutation, and potential novel targets for antimicrobial therapy of strains that could be engineered to resistance to the only two effective agents, tetracyclines and chloramphenicol. Once the genomic sequences are determined and analyzed they will be made available to the research community through an online database with a number of tools to facilitate data retrieval. During the course of the project there will also be ongoing release of preliminary data.